Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model
Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model
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DOI：
10.1002/mc.20094
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发表时间：
2006-05-01
影响因子：
4.6
通讯作者：
Miwa, M
中科院分区：
文献类型：
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作者：
Loilome, W;Yongvanit, P;Miwa, M
肝吸虫感染引起的胆管癌是泰国东北部最常见和最严重的疾病之一。为了阐明Ov感染诱导胆管癌发生的分子机制，我们采用Ov和N-亚硝基二甲胺诱导的仓鼠CCA模型，利用荧光差异显示-PCR技术分析CCA相关候选基因。通过反向北方微阵列杂交证实了在我们鉴定的149条差异扩增条带中，与CCA仓鼠相关的23个转录本上调和1个转录本下调。上调的基因包括信号转导蛋白激酶A调节亚基I α（Prkar 1a）、豆蔻酰化富含丙氨酸的蛋白激酶C底物、转录因子LIM-4-only结构域、参与脂质代谢的氧固醇结合蛋白、剪接调节蛋白9、参与蛋白降解的泛素缀合酶、P微管蛋白、P肌动蛋白和VI型胶原。实时荧光定量PCR结果显示，Prkar 1a在CCA及其前病变组织中的表达明显高于正常肝、胆囊上皮（P < 0.05）。Prkar 1 a表达随胆管增生、癌前病变向癌的进展而沿着增高。这些发现有助于我们了解CCA分子致癌过程，为未来开发新的化疗药物提供独特的视角。(c)2006 Wiley-Liss，Inc.
Cholangiocarcinoma (CCA) induced by liver fluke (Opisthorchis viverrini, Ov) infection is one of the most common and serious disease in northeast Thailand. To elucidate the molecular mechanism of cholangiocarcinogenesis induced by Ov infection, we employed a hamster model of CCA induced by Ov and N-nitrosodimethylamine and analyzed candidate genes involved in CCA using fluorescence differential display-PCR. Of 149 differentially amplified bands we identified, the upregulation of 23 transcripts and downregulation of 1 transcript related to CCA hamsters were confirmed by a reverse northern macroarray blot. The upregulated genes include signal transduction protein kinase A regulatory subunit I alpha (Prkar1a), myristoylated alanine-rich protein kinase C substrate, transcriptional factor LIM-4-only domain, oxysterol-binding protein involved in lipid metabolism, splicing regulatory protein 9, ubiquitin conjugating enzyme involved in protein degradation, P tubulin, P actin, and collagen type VI. Quantitative real-time PCR confirmed that the expression of Prkar1a was significantly higher in CCA and its precursor lesion when compared with normal liver and normal gall bladder epithelia (P < 0.05). Prkar1a expression tended to increase along with the progression of biliary transformation from hyperplasia and precancerous lesions to carcinoma. These findings contribute to our understanding of the processes involved in the molecular carcinogenesis of CCA in order to provide a unique perspective on the development of new chemotherapeutics in future. (c) 2006 Wiley-Liss, Inc.